rs1978095

chr7-87622325-A-Gchr7-87622325-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000265724.8(ABCB1):c.-330-21247T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 151,598 control chromosomes in the GnomAD database, including 226 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.021 (226 hom., cov: 32)
• Consequence: ABCB1 ENST00000265724.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

Genes affected

ABCB1 (HGNC:40): (ATP binding cassette subfamily B member 1) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs. This protein also functions as a transporter in the blood-brain barrier. Mutations in this gene are associated with colchicine resistance and Inflammatory bowel disease 13. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB1	NM_000927.5	c.-330-21247T>C		intron_variant
ABCB1	NM_001348944.2	c.-183-21247T>C		intron_variant
ABCB1	NM_001348945.2	c.-154-19185T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB1	ENST00000265724.8	c.-330-21247T>C		intron_variant		1		P1
ABCB1	ENST00000416177.1	c.-183-21247T>C		intron_variant		5
ABCB1	ENST00000543898.5	c.-330-21247T>C		intron_variant		5
ABCB1	ENST00000476862.1	n.136-19185T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3157 AN: 151492 Hom.: 225 Cov.: 32

Gnomad AFR AF: 0.0267

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0360

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00101

Gnomad OTH AF: 0.0158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0209 AC: 3169 AN: 151598 Hom.: 226 Cov.: 32 AF XY: 0.0221 AC XY: 1641 AN XY: 74136

Gnomad4 AFR AF: 0.0268

Gnomad4 AMR AF: 0.0360

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.00603

Gnomad4 NFE AF: 0.00101

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.00727 Hom.: 49

Bravo AF: 0.0254

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	7.1
Dann	Benign	0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1978095; hg19: chr7-87251641;